A Pharmacokinetic Study to Access How the Body Absorbs and Removes Linifanib in Male Patients With Advanced Solid Tumors.

Disposition of [14C]ABT-869 in Patients With Solid Tumors Following a Single Oral Dose Administration

A pharmacokinetic study to access how the body absorbs and removes linifanib in male patients with advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: [14C]linifanib; Drug: ABT-869, linifanib

Detailed Description

This study is designed to assess the mass balance of [14C]linifanib and the metabolic profiles of linifanib in 4 subjects with advanced solid tumors following a single oral dose. Subjects may continue on linifanib after completion of the metabolism study. The results of this study will determine the exposure of major metabolites and excretion pathway(s) of the parent drug and metabolites of linifanib in humans.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Site Reference ID/Investigator# 40942
    • Cleveland, Ohio, United States, 44195
      • Site Reference ID/Investigator# 53663

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria

• Subject must be >/= 18 years of age.
• Subject must have a histologically or cytologically confirmed non-hematologic malignancy.
• Eastern cooperative Oncology Group (ECOG) Performance Score of 0 to 2.
• Subject must have adequate bone marrow, renal and hepatic function.
• Subject must have Partial Thromboplastin Time (PTT) </= 1.5 x Upper Limit of Normal (ULN) and International Normalized Ratio (INR) </= 1.5.
• Subject must be capable of understanding and complying with parameters as outlined in the protocol and able to sign the informed consent.

Exclusion Criteria

• Subject has received previous administration of a radiolabeled research substance within 12 months prior to Study Day 1 or exposure to significant radiation (e.g., barium meal, etc.) within the past 3 months or within a period defined by 5 half-lives, whichever is shorter, prior to Study Day 1.
• Subject has received anti-cancer therapy including investigational agents, cytotoxic chemotherapy, radiation, hormonal or biologic therapy within 21 days or within a period defined by 5 half-lives, whichever is shorter, prior to Study Day 1.
• Subject is currently using a known inhibitor (e.g., ketoconazole) or inducer (e.g., rifampin) of cytochrome P450 3A (CYP3A) within 1 month prior to Study Day 1.
• Subject has not recovered to less than or equal to grade 1 clinically significant adverse effects/toxicities of the previous therapy.
• Subject has undergone major surgery within 21 days of Study Day 1.
• The subject has brain or meningeal metastases.
• The subject has non-small cell lung cancer (NSCLC) with a predominant squamous cell histology.
• Subject is receiving therapeutic anticoagulation therapy.
• Subject has a history of/or currently exhibits clinically significant events of bleeding (e.g., hemoptysis).
• Subject has proteinuria Common Terminology Criteria (CTC) Grade > 2 at baseline.
• Subject currently exhibits symptomatic or persistent, uncontrolled hypertension.
• Subject has a history of myocardial infarction within 6 months.
• Subject has known autoimmune disease with renal involvement.
• Subject is receiving combination anti-retroviral therapy for human immunodeficiency virus (HIV).
• Clinically significant uncontrolled conditions/medical symptoms.
• Subject has a documented left ventricular (LV) ejection fraction < 50%.
• Subject has previously received linifanib.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADME; [14C]linifanib	Drug: [14C]linifanib; [14C]linifanib, single administration, oral liquid
Experimental: Extension; linifanib	Drug: ABT-869, linifanib; linifanib once a day (QD), oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Profile	Blood samples for the pharmacokinetics (PK) of linifanib will be collected at designated time points.	Various timepoints from Day 1 through approximately Day 9
Total radioactivity	Blood, urine, and fecal samples for total radioactivity analysis will be collected at designated time points.	Various timepoints from Day 1 through approximately Day 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (Number of subjects with adverse events and/or dose-limiting toxicities)	Adverse event monitoring, lab test assessments, physical exam and vital signs will be evaluated throughout the study.	At each treatment visit (daily for first 9 days and then approximately every 4 weeks through end of treatment)

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Mark D. McKee, MD, Abbott

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: January 28, 2011
• First Submitted That Met QC Criteria: January 28, 2011
• First Posted (Estimate): February 1, 2011

Study Record Updates

• Last Update Posted (Estimate): September 21, 2012
• Last Update Submitted That Met QC Criteria: September 19, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: M10-966